Polymer factor IX moiety conjugates
View Patent ↗Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is polyethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.
1. A composition comprising a plurality of polyethylene glycol (PEG)-Factor IX moiety conjugates, the conjugates comprising a branched polyethylene glycol covalently attached via a spacer moiety comprised of one or more atoms to a Factor IX moiety that is either Factor IX or Factor IXa, where at least about 85% of the polyethylene glycol-Factor IX moiety conjugates in the composition are monoPEGylated.
2. The composition of claim 1 , wherein the branched polyethylene glycol comprises two polyethylene glycol chains attached to a polyol core.
3. The composition of claim 2 , wherein the polyol core is a glycerol core.
4. The composition of claim 3 , wherein the branched polyethylene glycol has a weight average molecular weight of about 40,000 daltons.
5. The composition of claim 4 , wherein the branched polyethylene glycol comprises two polyethylene glycol chains each having a weight average molecular weight of about 20,000 Daltons.
6. The composition of claim 1 , wherein the spacer intervening between the Factor IX moiety and the polyethylene glycol chains comprises a carbamate group.
7. The composition of claim 1 , where at least about 95% of the polyethylene glycol-Factor IX moiety conjugates in the composition are monoPEGylated.
8. The composition of claim 1 , wherein at least about 99% of the conjugates in the composition have from one to two of the branched polyethylene glycols covalently attached to the Factor IX moiety.
9. The composition of claim 1 , wherein the branched polyethylene glycol is covalently attached to the Factor IX moiety via an amide linkage.
10. The composition of claim 1 , wherein the Factor IX moiety is Factor IX.
11. The composition of claim 1 , wherein the Factor IX moiety is Factor IXa.
12. The composition of claim 1 , wherein the Factor IX moiety is recombinantly derived.
13. The composition of claim 1 , wherein the Factor IX moiety is blood-derived.
14. The composition of claim 3 , wherein the spacer intervening between the Factor IX moiety and the glycerol core of the branched polyethylene glycol comprises the structure:
wherein
(a) is either zero or one;
X, when present, is a spacer moiety comprised of one or more atoms;
(b′) is zero or an integer having a value of one through ten;
(c) is an integer having a value of one through ten;
R 2 , in each occurrence, is independently H or an organic radical;
R 3 , in each occurrence, is independently H or an organic radical; and
F9 is a Factor IX moiety.